1. Introduction to Lung Infections

1.1 Overview

• Respiratory infections are broadly classified by anatomical site, spanning the upper airways (nose, pharynx, larynx) down to the alveoli.
• Mild infections (e.g. common cold, acute bronchitis) are extremely common and usually self-limiting.
• More severe infections (e.g. pneumonia) pose significant morbidity and mortality risk worldwide.

Table 1.1 – Respiratory Infection Syndromes

1.2 Classification: Upper vs Lower Respiratory Tract

• Upper Respiratory Tract Infections (URTIs)
  • Rhinitis (common cold)
  • Pharyngitis, Laryngitis, Tonsillitis (sore throat syndromes, often overlapping with rhinitis)
• Lower Respiratory Tract Infections (LRTIs)
  • Bronchitis and Tracheitis
    • Leading cause of acute cough syndromes in adults
    • Major driver of exacerbations in COPD or bronchiectasis
  • Bronchiolitis (primarily in children caused by RSV; less common in adults)
  • Pneumonia
    • Community-acquired pneumonia (CAP)
    • Hospital-acquired pneumonia (HAP)
    • Ventilator-acquired pneumonia (VAP)
    • Pneumonia in immunocompromised hosts
    • Lung abscess, subacute infections, and tuberculosis
  • Pleural Infections (parapneumonic effusions, complicated effusions, empyema)

1.3 Microbiology: Common Pathogens

1. Viruses
   • Influenza A, B, C (cause seasonal flu, may exacerbate chronic disease or lead to pneumonia)
   • Respiratory syncytial virus (RSV), parainfluenza, rhinovirus, adenovirus (URTIs, bronchiolitis, some pneumonia)
   • Cytomegalovirus (CMV), varicella-zoster virus (rare, typically in immunocompromised)
2. Bacteria
   • Streptococcus pneumoniae: leading cause of community-acquired pneumonia
   • Haemophilus influenzae and Moraxella catarrhalis: bronchitis, COPD exacerbations
   • Staphylococcus aureus: can cause aggressive pneumonia, empyema; includes MRSA
   • Legionella pneumophila, Chlamydophila pneumoniae, Mycoplasma pneumoniae: ‘atypical’ pneumonia
   • Gram-negative bacilli (e.g. Klebsiella) more common in HAP or immunocompromised
   • Pseudomonas aeruginosa: HAP, VAP, bronchiectasis, CF
   • Mycobacterium tuberculosis and non-tuberculous mycobacteria: TB and subacute infections
3. Fungi
   • Aspergillus: mycetomas, allergic bronchopulmonary aspergillosis, pneumonia in immunosuppression
   • Pneumocystis jirovecii (PCP): pneumonia in severely immunocompromised patients
   • Histoplasma, Coccidioides, Blastomycetes: geographical ‘endemic’ mycoses (Ohio River valley, southwestern USA, etc.)

Table 1.2 – Common Respiratory Microbial Pathogens

†‘Atypical’ pneumonia organisms

1.4 Pathogenesis

• Inhalation of droplets containing pathogens (e.g. influenza, Mycobacterium tuberculosis)
• Microaspiration from the oropharynx or upper respiratory tract (e.g. S. pneumoniae, H. influenzae)
• Direct extension from contiguous sites (e.g. infected pleural fluid)
• Haematogenous spread from remote infection sites (e.g. S. aureus from right-sided endocarditis)

1.5 Clinical Presentations

• URTIs: sore throat, nasal congestion, coryza, mild fever.
• Bronchitis: cough ± sputum, mild dyspnoea, wheeze.
• Pneumonia: fever, productive cough (purulent/rusty sputum), dyspnoea, chest pain, focal chest signs (e.g. crackles).
• Severe Infections: respiratory failure, sepsis, or complications like pleural effusion/empyema.

1.6 Diagnosis

1. Clinical Assessment
   • History of symptoms (onset, sputum colour), exposures, comorbidities.
   • Examination: vital signs (fever, tachypnoea), chest auscultation, signs of pleural effusion.

Table 1.3 – Common Microbiological Tests for Respiratory Pathogens

* Skin test (Mantoux or Heaf) may also be positive if the patient had prior BCG vaccination.

1. Investigations
   • Chest X-Ray: identifies consolidation, infiltrates, cavitation, effusions.
   • Blood Tests: FBC, inflammatory markers (CRP), culture in severe disease.
   • Microbiological Sampling: sputum culture, nasopharyngeal swabs (for viruses), bronchoalveolar lavage, or pleural fluid analysis.
   • Microbial Identification: Gram stain, culture, nucleic acid amplification tests, antigen/antibody assays (Table 8.6).
2. Severity Assessment (e.g. CURB-65 for pneumonia, see subsequent topics).

Table 1.4 – Microbiological Diagnostic Tests: Advantages & Disadvantages

1.7 Management (Overview)

• Supportive Therapy
  • Adequate hydration, antipyretics, oxygen if hypoxic, analgesics for chest pain.
  • Consider hospital admission if severe infection or comorbidities.
• Antimicrobial Treatment
  • Determined by likely pathogens (Table 8.5).
  • Examples:
    • CAP: ß-lactam (e.g. amoxicillin) or combination with macrolide if atypical suspected.
    • Influenza: neuraminidase inhibitors (oseltamivir) in severe cases or high-risk groups.
    • Tuberculosis: multi-drug anti-TB regimens for 6 months or longer.

Table 1.5 – Drug Treatment of Respiratory Pathogens

†‘Atypical’ pneumonia organisms

• Prevention
  • Vaccination: influenza vaccine annually, pneumococcal vaccine, BCG for TB in high-prevalence areas.
  • Infection Control Measures: hand hygiene, isolation if needed (e.g. hospital settings).

1.8 Summary

• Diagnosis combines clinical, radiological, and microbiological approaches, guiding targeted therapy for optimal outcome.
• Respiratory infections are common, with presentations ranging from mild colds to life-threatening pneumonia or tuberculous disease.
• Microbial aetiology is broad, but a few pathogens (influenza, S. pneumoniae, M. tuberculosis) cause the majority of severe disease.

2. Upper Respiratory Tract Infection, Tracheitis, and Bronchitis

2.1 Epidemiology

• Extremely common: Many people experience at least one URTI or episode of bronchitis each year.
• Infants & children: Often have multiple URTIs per year.
• Exceptions (rare but severe):
  • Acute epiglottitis
  • Diphtheria
  • Whooping cough (pertussis)

2.2 Aetiology

• Viruses are the predominant cause (e.g. influenza, respiratory syncytial virus, parainfluenza).
• Bacterial causes (less frequent but often clinically significant):
  • Haemophilus influenzae: acute epiglottitis
  • Corynebacterium diphtheriae: diphtheria
  • Bordetella pertussis: whooping cough
  • Streptococcus pneumoniae and Haemophilus influenzae: bronchitis in chronic lung disease
• Vaccination prevents some serious causes (influenza A, diphtheria, whooping cough).

2.3 Pathogenesis

• Viral or bacterial infection of the upper airways → inflammation → increased mucus, cough, congestion.
• Diphtheria: Toxin-mediated damage → pharyngeal pseudomembrane → potential airway obstruction.
• Acute epiglottitis: Marked epiglottic swelling → risk of upper airway obstruction.
• Bronchitis: Infection and inflammation of bronchi/trachea → cough ± sputum, often mild.

Clinical Pearl
Differentiating mild infections (URTI, bronchitis) from pneumonia is vital. Fever, pleuritic chest pain, increased respiratory rate, focal chest signs, and hypoxia suggest pneumonia, requiring antibiotic therapy.

2.4 Common Pathogens by Site

The table below outlines typical pathogens for infections of the upper respiratory tract, bronchi, and bronchioles.

Table 2.1 – Common Pathogens in Upper Airway & Bronchial Infections

Note: RSV = Respiratory Syncytial Virus

2.5 Clinical Features

1. Rhinitis: Nasal discharge, sneezing (‘common cold’).
2. Pharyngitis, Tonsillitis, Laryngitis: Sore throat, possible visible pharyngeal erythema/pus, tonsillar enlargement, cervical lymphadenopathy.
3. Bronchitis / Tracheitis
   • Cough (may be purulent if bacterial).
   • Usually no focal chest signs unless exacerbating chronic lung disease.
   • Variable fever, malaise, anorexia.
4. Whooping Cough (Pertussis): Prolonged cough (up to ~12 weeks) with characteristic inspiratory whoop.
5. Diphtheria / Acute Epiglottitis: May present with stridor, drooling, or respiratory distress due to upper airway obstruction; can be life-threatening.

2.6 Diagnostic Approach & Management

2.6.1 Diagnosis

• Clinical: Usually obvious from history and examination.
• Microbiological:
  • Throat swabs or sputum culture (rarely needed unless severe or atypical).
  • Chest X-ray: To exclude pneumonia if suspected (persistent fever, pleuritic chest pain, low oxygen saturations, etc.).

2.6.2 Indications for Antibiotics

1. Diphtheria (requires intravenous antitoxin + antibiotics).
2. Acute epiglottitis (urgent antibiotic therapy).
3. Bronchitis in:
   • Chronic lung disease (COPD, bronchiectasis).
   • Immunocompromised patients.
   • Severe bacterial infection.
4. Whooping cough (Bordetella pertussis).

Key Point: Most simple URTIs/bronchitis are self-limiting, but acute epiglottitis, diphtheria, and suspected pneumonia always warrant immediate antibiotic therapy.

2.7 Prognosis

• Self-Limiting: Most infections resolve within ~10 days.
• Rheumatic Fever / Glomerulonephritis: Rare complication of Streptococcus pyogenes pharyngitis.
• Serious Causes:
  • Diphtheria: Historically up to 50% mortality in epidemics.
  • Acute epiglottitis: Potentially fatal airway obstruction if untreated.
  • Influenza: Usually mild, but in the elderly or those with chronic illnesses, can lead to significant mortality via pneumonia or decompensation of comorbidities.

3. Bronchiolitis

3.1 Epidemiology

• Most common LRTI in infants: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalisation in infancy.
• Age group: Typically affects children under 2 years, peaking between 3 and 6 months of age.
• Adults: Bronchiolitis is rare; usually caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae or respiratory viruses, often alongside bronchitis or pneumonia.

3.2 Aetiology & Pathogenesis

• Aetiology:
  • RSV is the primary cause of bronchiolitis in infants.
  • M. pneumoniae, C. pneumoniae and respiratory viruses can cause bronchiolitis-like illness in adults.
• Pathogenesis:
  • Viral infection → inflammation of bronchioles → increased mucus + oedema → partial or complete small airway obstruction.
  • Infants are more susceptible due to smaller airway calibre.

3.3 Clinical Features

• In Infants:
  • Cough, wheeze, and dyspnoea (laboured breathing).
  • Widespread wheezing + inspiratory crackles heard on auscultation.
  • May present with feeding difficulties, irritability, or dehydration due to increased work of breathing.
• In Adults:
  • Rarely isolated bronchiolitis; often part of bronchitis or pneumonia.

3.4 Diagnostic Approach

• Clinical diagnosis: Usually based on history (age, season) and examination (wheeze, fine crackles).
• Chest X-ray: Often normal; may show hyperinflation, bronchial wall thickening, or patchy atelectasis.
• Microbiological tests: RSV detection in nasopharyngeal aspirates is common (e.g. by immunofluorescence or nucleic acid tests).

3.5 Management

3.5.1 Assessing Severity

• Assess the infant for signs of respiratory distress, hydration status, and oxygenation. 

Table 3.1 – Indicators of Severe Bronchiolitis

3.5.2 Immediate Care

• Supplementary oxygen: If oxygen saturation < 92%.
• Supportive therapy:
  • Ensure adequate hydration (oral/NG/IV fluids if needed).
  • Treat fever/distress with paracetamol or ibuprofen.
  • Bronchodilators (e.g. nebulised ß₂-agonists) sometimes trialled, though effectiveness is variable.
  • Antibiotics only for suspected secondary bacterial infection.

3.5.3 Outpatient Management

• If hospital admission is not required:
  • Self-care advice:
    • Continue feeding/breastfeeding; ensure adequate fluids.
    • Paracetamol or ibuprofen for distress due to fever (avoid using both simultaneously).
    • Monitor for worsening: increased RR, poor feeding, or reduced wet nappies.
    • Avoid tobacco smoke exposure in the home.

3.6 Prognosis

• Good outcome if managed supportively; severe respiratory compromise is uncommon but can occur in infants with underlying risk factors (e.g. prematurity).
• Mostly self-limiting: ~5% of infants may need hospital admission.
• Future risk: RSV bronchiolitis can predispose to childhood asthma.

4. Community-Acquired Pneumonia

4.1 Epidemiology

• The incidence of CAP is 2–5 per 1000 population per year (some sources report 5–11 per 1000), and it increases significantly in children under 5 years old, the elderly (≥65 years), and those with comorbidities.
• CAP is the most common severe respiratory infection acquired outside hospital settings.
• Mortality in patients admitted to hospital with CAP ranges from 5–10% (though some audits suggest it can be over 20%). It may rise to ≥25% for patients with septicaemia or requiring intensive care.

4.2 Aetiology

• Definition: CAP is an acute infection of the alveoli, with clinical and radiological evidence of consolidation, acquired while not in hospital.
• Most common microbial causes:
  • Streptococcus pneumoniae (often cited as the single most common cause).
  • Influenza A virus.
  • So-called ‘atypical’ bacteria: Mycoplasma pneumoniae and Chlamydophila (Chlamydia) pneumoniae.
• Other possible pathogens include:
  • Haemophilus influenzae
  • Moraxella catarrhalis
  • Staphylococcus aureus (including MRSA)
  • Gram-negative bacilli (e.g. Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa)
  • Legionella pneumophila
  • Anaerobes (particularly in aspiration pneumonia)

Note: Viral causes and mixed infections can occur, especially with influenza.

4.3 Risk Factors

Risk factors for developing CAP include:

1. Extremes of age
   • Children under 5 years
   • Elderly (≥65 years, with risk rising further with increasing age)
2. Impaired consciousness or swallowing
   • Alcohol intoxication, drug overdose, sedation
   • Neurological disorders affecting swallowing (e.g. stroke, bulbar palsies)
   • Poor cough or gag reflex (risk of aspiration)
3. Chronic illness or immunocompromise
   • Diabetes mellitus (especially if poorly controlled)
   • Chronic respiratory conditions (e.g. COPD, bronchiectasis, cystic fibrosis)
   • Cardiac failure
   • Chronic liver or renal disease
   • HIV/AIDS or other causes of severe immunosuppression
   • Malnourishment
4. Lifestyle factors
   • Smoking
   • Poor dental hygiene (increased risk of aspiration of oropharyngeal anaerobes)
5. Recent hospital stay (though true CAP is by definition acquired outside hospital, any previous hospital admission can predispose to resistant organisms if pneumonia occurs soon after discharge).

4.4 Clinical Features

4.4.1 Symptoms

• Systemic: Fever, rigors, malaise, anorexia.
• Respiratory:
  • Cough (often productive of purulent sputum; can be ‘rusty’ when blood-tinged).
  • Dyspnoea (shortness of breath).
  • Pleuritic chest pain (sharp pain worsened by inspiration).
• Duration: Symptoms typically develop over <3 weeks, often 2–3 days.
• In some cases (especially in the elderly), no clear respiratory symptoms may be present; confusion or general deterioration might be the only clue.

4.4.2 Signs

• General: Pyrexia (fever), tachycardia, tachypnoea, potential hypotension in severe cases.
• Respiratory signs:
  • Increased respiratory rate and signs of respiratory distress (use of accessory muscles, nasal flaring, etc.).
  • Central cyanosis in severe cases.
  • Reduced expansion over the affected area(s).
  • Dullness to percussion (especially if there is a pleural effusion).
  • Bronchial breathing or coarse crepitations over the consolidated area.
  • Possible pleural rub if there is pleural involvement.
• Confusion or altered mental status can occur, especially in the elderly or if hypoxia is severe.
• Herpes labialis (‘cold sores’) may appear in some patients and can be associated with pneumococcal infections.

4.5 Diagnostic Approach

• Definition of CAP: Evidence of infection (fever, raised inflammatory markers, etc.) plus new consolidation on chest X-ray.

1. Clinical Assessment
   • History and physical examination to identify features of consolidation.
   • Assess severity (e.g. confusion, hypotension, high respiratory rate).
2. Investigations
   • Chest X-ray
     • Identifies consolidation and helps confirm the diagnosis.
     • Excludes alternative diagnoses (e.g. pulmonary oedema).
     • Detects complications such as pleural effusion, lung abscess, or cavitation.
   • Oxygen Saturation and Blood Gases
     • Pulse oximetry (oxygen saturation) and/or arterial blood gas (ABG) analysis.
     • Assesses the degree of hypoxia and guides oxygen therapy.
   • Blood Tests
     • Full blood count (FBC): Can show raised or lowered white cell count.
     • C-reactive protein (CRP): Usually >50 mg/L in CAP; helps monitor inflammatory response and treatment effectiveness.
     • Urea and electrolytes (U&E): Elevated urea is a component of the CURB-65 score (marker of severity). Low sodium can sometimes occur in severe CAP.
     • Liver function tests (LFTs): May be transiently abnormal in severe cases.
     • Glucose and clotting profile: To identify any metabolic derangement or coagulopathy.
   • Microbiological Tests
     • Blood cultures: Positive in ~20% of inpatients; indicates severe disease (septicaemia).
     • Sputum culture (and Gram stain if available): Helps identify bacterial pathogens, although atypical organisms may be missed.
     • Urinary antigen tests: Useful for rapid identification of Legionella pneumophila or Streptococcus pneumoniae.
     • Nasopharyngeal aspirates or swabs: Can detect respiratory viruses (e.g. influenza) via PCR or viral culture.
   • Additional or Specialised Tests
     • HIV test: If there is suspicion of immunocompromise or if Pneumocystis jirovecii infection is considered.
     • Pleural ultrasound ± pleural aspiration: To identify and sample pleural effusions or empyema.
     • Computed Tomography (CT) scan: May be required if the diagnosis is uncertain or if complications are suspected (e.g. empyema, abscess).
     • Bronchoscopy: Considered if there is persistent lobar collapse, suspicion of obstructing tumour, or non-resolving consolidation.
3. Differential Diagnosis
   • Other lung infections (e.g. Pneumocystis jirovecii pneumonia in immunocompromised patients; tuberculosis).
   • Non-infectious causes of lung shadowing (e.g. pulmonary embolism with infarction, malignancy, pulmonary oedema, vasculitis).

4.6 Immediate Management

1. Assess Severity
   • Commonly by the CURB-65 score (Confusion, Urea >7 mmol/L, Respiratory rate ≥30/min, BP <90/60 mmHg, Age ≥65).
   • Score guides whether outpatient management is safe (score 0–1) or if hospital/ICU admission is needed (score ≥3).
2. Antibiotic Therapy
   • Empirical antibiotics are started promptly (first dose as soon as possible).
   • Choice is based on local guidelines, severity (e.g. CURB-65), and likely pathogens – the below table is an example of how

1. Supportive Care
   • Oxygen therapy to maintain saturations >94–95%. High-flow oxygen or mechanical ventilation may be required for severe hypoxia.
   • IV fluids for hypotension or poor oral intake. In cases of septic shock, inotropes may be required.
   • Analgesia (non-steroidal anti-inflammatory drugs or paracetamol) for pleuritic pain and to reduce fever.

4.7 Long-Term Management

1. Follow-up
   • Clinical review to ensure resolution of symptoms and improvement in inflammatory markers.
   • A repeat chest X-ray (often at ~6 weeks) is recommended, especially in older patients or smokers, to ensure resolution of consolidation and to exclude underlying malignancy or other pathologies.
2. Vaccination and Prevention
   • Pneumococcal vaccination (for children, adults ≥65 years, and other at-risk groups such as those with chronic diseases).
   • Influenza vaccination annually in at-risk groups.
3. Lifestyle Modifications
   • Smoking cessation.
   • Alcohol reduction if relevant.
4. Management of Comorbidities
   • Optimise control of chronic conditions (e.g. diabetes, heart failure, COPD) to reduce the risk of recurrent infections.

4.8 Prognosis/Complications

• Prognosis:
  • Most patients improve within 72 hours of appropriate antibiotic therapy, becoming apyrexial and less hypoxic.
  • Mortality ~5–10% in hospitalised CAP, with some data suggesting rates >20% in certain cohorts. Rates rise with septicaemia, multi-lobar involvement, or need for intensive care.
• Complications:
  • Respiratory failure (Type I or Type II).
  • Septic shock (hypotension, lactic acidosis).
  • Parapneumonic effusion or empyema (infection in the pleural space; often requires drainage).
  • Lung abscess or cavitation.
  • ARDS (acute respiratory distress syndrome) in severe cases.
  • Metastatic infection (e.g. septic arthritis, endocarditis) is rare.
  • Clostridioides difficile diarrhoea (secondary to broad-spectrum antibiotic use).
  • Persistent consolidation that does not resolve within expected time frames may necessitate further investigations (e.g. to exclude bronchial obstruction by a neoplasm).

5. Hospital-Acquire Pneumonia (HAP) & Ventilator-Acquired Pneumonia (VAP)

5.1 Epidemiology

• Hospital-acquired pneumonia (HAP) is defined as pneumonia occurring >48 hours after hospital admission or within one week of discharge (in non-immunocompromised patients).
  • It is the most common fatal nosocomial infection.
• Ventilator-acquired pneumonia (VAP) is pneumonia arising >48 hours after endotracheal intubation in mechanically ventilated patients.
  • The risk of VAP is approximately 1% per day of mechanical ventilation.
• Mortality for both HAP and VAP is around 30%, although many deaths are also related to the underlying illness.

5.2 Aetiology

• Different pathogenic profile compared with CAP:
  • Staphylococcus aureus (including MRSA)
  • Gram-negative bacilli (e.g. Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Enterobacter, and others)
  • Streptococcus pneumoniae or Haemophilus influenzae may still be involved, especially in early-onset HAP (<5 days since admission) when there is a lower risk of multi-drug resistant organisms.

5.3 Risk Factors

1. Hospitalisation
   • Extended stay in hospital or recent discharge increases exposure to resistant hospital flora.
2. Mechanical Ventilation
   • Intubation bypasses the upper airway’s defences, allowing direct entry of organisms into the lungs.
   • Sedation and recumbent positioning reduce cough reflex and increase risk of microaspiration.
3. Prior Antibiotic Use
   • Disrupts normal flora, fostering colonisation by Gram-negative bacteria or MRSA.
4. Invasive Devices
   • Nasogastric tubes increase risk of aspiration.
   • Central venous catheters (secondary risk via bloodstream infections, though more relevant to sepsis in general).
5. Proton Pump Inhibitors
   • Reduced gastric acidity can promote bacterial overgrowth, increasing aspiration risk.

5.4 Clinical Features

5.4.1 Symptoms

• Often similar to those seen in CAP:
  • Fever, purulent sputum, dyspnoea, pleuritic chest pain (though sometimes less pronounced or masked by sedation).
• Ventilator-Acquired Pneumonia:
  • May present as new fever, increasing oxygen requirements, new-onset crepitations on auscultation, and purulent secretions in the endotracheal tube.

5.4.2 Signs

• May include:
  • Tachypnoea, hypoxia (rising oxygen demand).
  • Tachycardia and hypotension if sepsis develops.
  • Fever (though patients may be normothermic or hypothermic).
• On auscultation:
  • Crepitations (crackles) over affected areas.
  • Signs of consolidation (similar to CAP), though sometimes difficult to detect in patients who are sedated or unable to cooperate.

5.4.3 Differential Diagnoses

In patients with suspected HAP or VAP, exclude:

• Lobar collapse (e.g. sputum plugging).
• Atelectasis (due to shallow breathing or inadequate inspiration).
• Pulmonary embolism (can cause hypoxia and fever).
• Fluid overload or cardiogenic pulmonary oedema (particularly on intensive care units where fluid balance can fluctuate).

5.5 Diagnostic Approach

• Generally similar to CAP, but CURB-65 does not apply for HAP or VAP.
• Clinical suspicion is often triggered by new infiltrates on chest X-ray plus systemic signs of infection.
• Investigations commonly used:
  1. Chest X-ray to identify new consolidation, effusion, or alternative diagnoses.
  2. Blood tests: Full blood count, CRP, urea & electrolytes, etc.
  3. Microbiological cultures:
     • Blood cultures (may be positive in severe infection).
     • Endotracheal aspirates (in VAP) or sputum cultures (in HAP), though colonisation can make interpretation difficult.
  4. Arterial blood gas / Pulse oximetry to assess oxygenation and guide respiratory support needs.
  5. Exclude other causes of deterioration (see differential diagnoses above).

5.6 Immediate Management

1. Antibiotic Therapy
   • Empirical regimens differ from CAP due to higher likelihood of Gram-negative bacteria or MRSA.
   • Choice depends on local policy, onset of pneumonia (early vs. late), and risk factors for multi-drug resistant organisms.
   • Examples (from provided data):
     • Early onset (<5 days) and no risk factors: cover Strep. pneumoniae, H. influenzae, Staph. aureus, and Gram-negative enterobacteria.
     • Late onset (≥5 days) or risk factors for MDR organisms: add coverage for MRSA (e.g. vancomycin/teicoplanin) and resistant Gram-negative bacilli (e.g. piperacillin-tazobactam, extended-spectrum cephalosporins, carbapenems).
2. Supportive Measures
   • Optimise oxygenation (mechanical ventilation settings in VAP, supplemental oxygen in HAP).
   • Adequate hydration: IV fluids may be needed, especially if septic.
   • Haemodynamic support for hypotension or shock (vasopressors if required).
3. General Preventive / Adjunctive Steps
   • Elevate the head of the bed (~30–45°) to reduce aspiration risk.
   • Minimise sedation if possible (to allow better cough reflex).
   • Physiotherapy (where appropriate) to aid secretion clearance.

5.7 Long-Term Management

• Prevention in future admissions:
  • Early mobilisation postoperatively.
  • Oral or oropharyngeal decontamination (e.g. chlorhexidine mouthwash).
  • Judicious use of proton pump inhibitors and nasogastric tubes.
  • If ventilated again in the future, attempt to reduce ventilation duration.
• Follow-up is less clearly defined than with CAP, but review of resolution and reconsideration of any chronic risk factors is prudent.

5.8 Prognosis/Complications

• Mortality ~30%. However, a significant proportion may be attributable to the underlying illness that necessitated prolonged hospital stay or mechanical ventilation.
• Complications:
• Acute respiratory failure requiring escalated ventilatory support.
• Septic shock and multi-organ failure.
• Further antibiotic resistance or Clostridioides difficile infection due to broad-spectrum antibiotic use.

6. Pneumonia in the Immunocompromised Patient

6.1 Epidemiology

• Pneumonia affects 25% of patients with neutropenia and ≥40% of bone marrow transplant recipients.
• Incidence is driven by the extent of immunosuppression (e.g. malignancies, organ transplants, chronic immunosuppressive therapy).
• HIV infection is widespread globally, with approximately 31 million individuals infected in 2009 and a particularly high prevalence in sub-Saharan Africa (1 in 20 affected).
  • In the United Kingdom and other high-income settings, risk is increased in men who have sex with men and in intravenous drug users.

6.2 Aetiology

• Broad range of pathogens due to compromised immune defences:
  • Bacterial (e.g. Streptococcus pneumoniae, Staphylococcus aureus, Gram-negative bacilli, Mycobacterium tuberculosis).
  • Fungal (e.g. Aspergillus species, endemic mycoses).
  • Viral (e.g. cytomegalovirus, respiratory viruses such as RSV or influenza).
  • Pneumocystis jirovecii (formerly Pneumocystis carinii).
  • Non-tuberculous mycobacteria (NTM), Nocardia.
• HIV-specific pathophysiology:
  • HIV infection leads to progressive loss of CD4 T-cells, reducing cell-mediated immunity.
  • As the CD4 count falls below 200 cells/μL, the risk of opportunistic infections (e.g. Pneumocystis pneumonia, CMV pneumonia) rises dramatically.
  • AIDS is defined by the presence of severe immunodeficiency and associated complications (e.g. Pneumocystis pneumonia, Kaposi’s sarcoma, or pulmonary lymphoma).

6.3 Risk Factors

1. Type of Immunodeficiency
   • Neutropenia: chemotherapy, aplastic anaemia, haematopoietic stem cell transplant (HSCT).
   • Defects in cell-mediated immunity: HSCT, lymphomas, long-term high-dose steroids, immunosuppression for organ transplants.
   • Antibody deficiency: multiple myeloma, chronic lymphocytic leukaemia, B-cell depletion therapy, common variable immunoglobulin deficiency.
   • HIV infection: highest risk when CD4 count <200 cells/μL.
2. Underlying Disease and Treatment
   • Frequent antibiotic use, which selects for resistant pathogens.
   • Concurrent malignancies or chronic inflammatory conditions requiring immunosuppression.
3. Exposure to HIV
   • Unprotected sexual intercourse, needle sharing, or vertical (mother-to-child) transmission.
   • Greatest global burden in sub-Saharan Africa.

6.4 Clinical Features

The exact presentation depends on the pathogen and the nature of the immune defect.

6.4.1 Bacterial Pneumonia

• Often rapid onset, with lobar consolidation and raised inflammatory markers (similar to HAP).
• Marked hypoxia can occur.

6.4.2 Fungal Pneumonias

• Aspergillus
  • Causes patches of consolidation or macronodules on imaging.
  • Presentation: fever, cough, and occasionally haemoptysis.
  • May spread to sinuses, brain, joints, or skin.

6.4.3 Pneumocystis Pneumonia (PCP)

• Characteristically gradual over 3–4 weeks.
• Dry cough, progressive dyspnoea, profound exertional desaturation.
• Mild pyrexia and few chest signs on auscultation (often disproportionate to the degree of hypoxia).

6.4.4 Viral Pneumonias

• Respiratory viruses (e.g. influenza, respiratory syncytial virus)
  • May start with upper respiratory tract symptoms, then progress to severe lower respiratory involvement (cough, dyspnoea).
  • Widespread crackles or wheeze on auscultation.
• Cytomegalovirus (CMV)
  • Reactivation in immunosuppressed individuals, with fever, cough, dyspnoea, and hypoxia.
  • Bilateral widespread infiltrates on imaging.

6.4.5 HIV-Specific Considerations

• Early HIV (CD4 >200 cells/μL): Tuberculosis, S. pneumoniae CAP, S. aureus, and other standard community or hospital pathogens.
• CD4 <200 cells/μL: Significantly increased risk of opportunistic infections (especially Pneumocystis pneumonia), pulmonary lymphoma, Kaposi’s sarcoma.

Clues to HIV infection in an undiagnosed patient might include oral candidiasis, hairy leukoplakia, or unusual chest X-ray findings (e.g. bilateral interstitial infiltrates with marked exertional hypoxia that does not respond to standard CAP therapy).

6.5 Diagnostic Approach

• Chest X-ray: Often non-specific; interstitial or nodular patterns depending on pathogen.
• CT scan: Can reveal characteristic patterns (e.g. halo/crescent sign for Aspergillus, ground-glass opacities for Pneumocystis).
• Laboratory Tests:
  • FBC, inflammatory markers, blood cultures.
  • Sputum analysis (culture, PCR).
  • Bronchoscopy ± biopsy if diagnosis remains unclear.
  • HIV serology (if HIV is suspected), plus CD4 count and viral load measurement.
• Exclude non-infectious aetiologies: Pulmonary oedema, acute respiratory distress syndrome (ARDS), alveolar haemorrhage, drug/radiation toxicity.

6.6 Immediate Management

1. Supportive Care
   • Oxygen to correct hypoxia.
   • IV fluids if hypotensive or septic.
   • Antipyretics for fever.
   • Reduce immunosuppression (if possible) to help immune recovery.
2. Empirical Antimicrobial Therapy
   • Often broad-spectrum or combined treatments targeting both typical and opportunistic organisms.
   • Tailor therapy once a specific pathogen is identified.
   • In HIV with severe immunosuppression, cover Pneumocystis early if clinically suspicious.

6.7 Long-Term Management

1. Prevention
   • Prophylaxis (antibacterial, antifungal, antiviral) for high-risk patients (e.g. prolonged neutropenia, low CD4 counts).
   • CMV-negative blood products or organs for patients without prior CMV exposure.
   • Needle exchange programmes and safe sex practices reduce HIV transmission.
2. HIV-Specific Care
   • Antiretroviral therapy (ART) to suppress viral load and increase CD4 count.
   • Monitor response via CD4 count and HIV viral load.
   • Regular screening for opportunistic infections (e.g. TB) and prophylaxis (e.g. co-trimoxazole for PCP when CD4 <200 cells/μL).
3. Follow-up
   • Repeat imaging to confirm resolution or identify complications.
   • Close monitoring for adverse drug effects (e.g. toxicity from antifungals or ART).

6.8 Prognosis and Complications

• Mortality varies by pathogen:
  • ≥30% with Aspergillus or CMV pneumonia.
  • ~10% for Pneumocystis pneumonia.
  • Lower for typical respiratory viruses, though infections may linger in immunosuppressed patients.
• Complications:
  • Dissemination of infection (Aspergillus to brain, Mycobacteria to other organs).
  • Respiratory failure or ARDS.
  • Ongoing immunosuppression and secondary infections.

6.9 Lung Complications of HIV

HIV itself does not directly damage the lung, but causes profound immunosuppression over time – this increases susceptibility to:

1. Infectious Complications (especially when CD4 <200 cells/μL)
   • Pneumocystis pneumonia (PCP)
   • Cytomegalovirus pneumonitis
   • Mycobacterium tuberculosis or non-tuberculous mycobacteria
   • Aspergillus species
   • Bacterial pneumonias (e.g. S. pneumoniae, S. aureus, Pseudomonas, H. influenzae)
2. Non-Infectious Complications
   • Chronic obstructive pulmonary disease and bronchiectasis
   • Pulmonary hypertension
   • Lung cancer
   • Kaposi’s sarcoma (herpes virus-related vascular tumours)
   • Non-Hodgkin lymphoma
   • Interstitial lung diseases (e.g. lymphocytic interstitial pneumonitis)

Key Points

• Long-term ART can significantly reduce the incidence of these pulmonary complications by preserving or restoring immune function.
• HIV pneumonia may present similarly to CAP, but lack of response to conventional antibiotics raises suspicion of an opportunistic pathogen (e.g. Pneumocystis).
• Oral candidiasis and other opportunistic infections are common co-markers in advanced HIV.

7. Complications of Pneumonia: Parapneumonic Effusions and Empyema

7.1 Epidemiology

• Parapneumonic effusions complicate about 7% of cases of community-acquired pneumonia (CAP).
• Empyema is relatively rare but can occur as a complication of pneumonia, prolonged chest drains, hospital-acquired pneumonia (HAP), or pleural procedures and surgery.
• Mortality associated with empyema is around 30%.

7.2 Aetiology

• Uncomplicated Parapneumonic effusions are sterile effusions arising in the context of pneumonia.
• Complicated parapneumonic effusions (CPE) occur when bacteria infect the pleural fluid (pH <7.2, turbid appearance, or positive culture).
• Empyema (pus in the pleural space) may be:
  • Community-acquired: Frequently caused by Streptococcus pneumoniae, S. milleri group, anaerobes, or Staphylococcus aureus.
  • Hospital-acquired: Commonly Staphylococcus aureus (often MRSA), Pseudomonas aeruginosa, Gram-negative bacilli, and occasionally anaerobes.

Pathogenesis

1. Parapneumonic effusion: Pneumonic consolidation inflames the pleura, producing an exudative effusion that is initially sterile.
2. Complicated parapneumonic effusion or empyema: Bacteria invade the pleural space, provoking inflammation, fibrin deposition, and adhesions between visceral and parietal pleura. Fluid may become loculated, hindering drainage.
3. Frank empyema: Pus in the pleural fluid (turbid, often with high white cell count).

7.3 Risk Factors

• Under-treated or severe pneumonia (especially CAP).
• Prolonged hospital stay, particularly in patients with chest drains or recent thoracic surgery.
• Immunocompromise or chronic debilitating conditions.
• Aspiration risk (e.g. altered consciousness, poor dentition).
• Poor antibiotic penetration or inadequate treatment, allowing infection to extend into the pleural space.

7.4 Clinical Features

• Symptoms:
  • Fever, anorexia, malaise.
  • Pleuritic chest pain, breathlessness (dyspnoea).
• Signs:
  • Pyrexia and signs of a pleural effusion on examination (diminished breath sounds, stony dull percussion note, reduced expansion on the affected side).
• Laboratory Clues:
  • Normocytic, normochromic anaemia.
  • Increased platelet count.
  • Reduced albumin.
  • Increased C-reactive protein (CRP).

• High suspicion: Any patient with pneumonia (or other evidence of infection) plus a pleural effusion, especially if loculated on imaging.

7.5 Diagnostic Approach

1. Imaging
   • Chest X-ray: May show a pleural effusion.
   • Pleural ultrasound: Particularly sensitive for detecting loculations and guiding pleural aspiration or drainage.
   • CT scan: Can confirm loculated fluid, pleural thickening, or other underlying pathology.
2. Pleural Aspiration (‘Tap’)
   • Appearance: Turbid/yellow fluid or frank pus suggests infection.
   • Laboratory Tests on pleural fluid:
     • pH <7.2 is highly suggestive of infected fluid (e.g. empyema).
     • Glucose often low; LDH often high.
     • Culture (bacteriology) or Gram stain may identify the organism.
   • Distinction between Transudates and Exudates often uses Light’s criteria (for typical pleural effusions).
     • However, in pneumonia-related effusions, an exudative pattern is usual.
3. Blood Tests
   • Elevated CRP, white cell count, or other inflammatory markers.
4. Differential Diagnosis
   • Pleural tuberculosis: Presents similarly (exudative effusion), but requires different antibiotics and usually does not need drainage.
   • Other causes of pleural effusions (e.g. malignancy, pulmonary embolism).

7.6 Immediate Management

• Parapneumonic Effusions (uncomplicated)
  • Often resolve spontaneously with appropriate treatment of pneumonia.
• Complicated Parapneumonic Effusion (CPE) or Empyema
  1. Antibiotics
     • Given for 3–6 weeks, guided by culture results and whether the infection is community- or hospital-acquired.
     • Common regimens include cover for Streptococcus, Staphylococcus aureus, Gram-negative bacilli, and/or anaerobes depending on local resistance patterns.
  2. Pleural Drainage
     • Insertion of a chest drain to remove infected fluid and improve lung re-expansion.
     • Loculations may hamper drainage; approximately 30% of patients require surgical intervention(e.g. video-assisted thoracoscopic surgery, VATS).
     • Intrapleural fibrinolytic therapy may be tried, though it is not universally effective.

7.7 Long-Term Management

• Monitoring:
  • Reassess clinically and with imaging to ensure resolution of fluid collections.
  • Measure inflammatory markers (CRP, white cell count) to confirm response to therapy.
• Address Underlying Cause:
  • Complete antibiotic course for pneumonia or underlying infection source.
  • Evaluate for risk factors (e.g. aspiration, comorbidity) to prevent recurrence.
• Pulmonary Rehabilitation if long hospital admission or persistent reduction in lung volumes.

7.8 Prognosis / Complications

• Mortality in empyema is around 30%.
• Prolonged hospital stay: CPE or empyema may add >1 week to admission length.
• Persistent Pleural Thickening: Can result in a restrictive lung defect and chronic breathlessness.
• Other Complications:
  • Recurrent effusions or loculations requiring repeat drainage.
  • Lung abscess (more information in topic 8)
  • Potential progression to sepsis if inadequately managed.

8. Subacute Lung Infections and Lung Abscess

8.1 Epidemiology

• Subacute lung infections evolve over weeks to months rather than days (as in acute pneumonia).
• Tuberculosis is the most common subacute infection worldwide (discussed separately).
• Lung abscesses can arise as complications of pneumonia, aspiration, or as part of these subacute infections.
• Exact incidence varies, but risk is heightened by aspiration, poor dental hygiene, immunocompromise, and inadequate treatment of preceding pneumonia.

8.2 Aetiology

1. Subacute Lung Infections
   • Predominantly caused by Mycobacterium tuberculosis (discussed elsewhere).
   • Other pathogens: Rare bacteria, fungi (e.g. Nocardia, endemic mycoses), or parasites.
2. Lung Abscess
   • Often secondary to:
     • Aspiration pneumonia (alcohol misuse, neurological swallowing disorders).
     • Inadequately treated pneumonia.
     • Bronchial obstruction (tumour, foreign body).
     • Pulmonary infarction or septic emboli (e.g. right-sided endocarditis in IV drug use).
     • Subphrenic or hepatic abscess tracking to the lung.

8.3 Risk Factors

• Aspiration risk (e.g. reduced consciousness, bulbar palsy, oesophageal disorders).
• Immunocompromise (e.g. HIV, prolonged steroid use, chemotherapy).
• Poor dentition (increasing anaerobic bacterial load).
• Underlying lung disease (e.g. bronchiectasis, COPD) or obstruction.
• Socioeconomic factors (e.g. crowded living conditions for TB transmission).

8.4 Clinical Features

8.4.1 Subacute Lung Infections

• Prolonged illness with low-grade fever, night sweats, malaise, weight loss.
• Cough often with purulent or occasionally blood-streaked sputum.
• Chest X-ray/CT: Focal consolidation and/or nodules, which may cavitate. Pleural effusions may be present.

8.4.2 Lung Abscess

• Foul-smelling purulent sputum in large quantities.
• Swinging fever, pleuritic chest pain, haemoptysis, malaise, weight loss.
• Examination: Possible clubbing, anaemia, and localised crepitations on auscultation.
• Imaging: Thick-walled cavity with an air–fluid level on chest X-ray or CT scan.

8.5 Diagnostic Approach

1. Imaging
   • Chest X-ray and CT can identify cavities, nodules, air–fluid levels, or associated effusions.
2. Microbiological Tests
   • Sputum analysis: Multiple sputum cultures, including tests for mycobacteria, anaerobes, fungi, and/or parasites.
   • Bronchoscopy or percutaneous biopsy: May be necessary to confirm the diagnosis and exclude non-infective causes (e.g. lung cancer, vasculitis, allergic bronchopulmonary aspergillosis).
3. Blood Tests
   • Full blood count (FBC): May show neutrophilia or anaemia of chronic disease.
   • Inflammatory markers: Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
   • Blood cultures if septicaemia or metastatic infection is suspected.
4. Differential Diagnoses
   • Tuberculosis, lung cancer, cavitating pulmonary emboli, vasculitis (e.g. granulomatosis with polyangiitis), or allergic bronchopulmonary aspergillosis (ABPA).

8.6 Immediate Management

1. Empirical Antibiotic Therapy
   • Often required for 3–6 weeks.
   • Should cover both strict anaerobes and facultative organisms (e.g. streptococci) when a lung abscess is suspected, or based on local guidelines if aspiration pneumonia is likely.
   • Tailor according to pathogen if identified (e.g. antifungals for fungal infection, specific drugs for mycobacteria).
2. Supportive Measures
   • Ensure adequate hydration and nutritional support.
   • Analgesia for pleuritic pain.
   • Postural drainage: Encourages expectoration of infected material (particularly in abscesses).

8.7 Long-Term Management

• Further Investigations if no improvement:
  • Repeat imaging and sputum studies.
  • Bronchoscopy or CT-guided biopsy to rule out obstruction or alternative diagnoses.
• Drainage or Surgical Intervention:
  • CT-guided drainage if abscess does not respond to antibiotics.
  • Surgical resection rarely, for persistent, large cavities or suspected neoplasm.

8.8 Prognosis / Complications

• Subacute Infections
  • Can progress to chronic debilitating states if untreated.
  • Risk of haemoptysis or significant lung destruction.
• Lung Abscess
  • May rupture into the pleural space, causing empyema.
  • Persistent cavity formation leading to bronchiectasis or structural lung changes.
  • In approximately 20–30% of cases, an empyema co-exists.
• Overall Outcome
  • Usually good with appropriate prolonged antibiotic therapy, though improvement may be slow.
  • Underlying risk factors (e.g. aspiration) must be addressed to prevent recurrence.

9. Tuberculosis

9.1 Epidemiology

• Most common fatal bacterial infection worldwide: ~9–10 million new cases annually.
• High global burden: ~30% of the world’s population has latent tuberculosis, with a risk of reactivation.
• Incidence varies greatly by region:
  • Highest in Asia and sub-Saharan Africa (often >100 per 100,000).
  • Lower in Europe and North America (<25 per 100,000), but certain urban areas (e.g. London) may reach ~50 per 100,000.
• Groups at higher risk in high-income countries include immigrants from high-incidence regions, drug users, prison inmates, and HIV-positive individuals.

9.2 Aetiology

• Caused by Mycobacterium tuberculosis or, less commonly, Mycobacterium bovis.
• Transmission: Inhalation of aerosolised droplets from infectious individuals with pulmonary TB.
• Pathogenesis:
  1. Primary infection may be asymptomatic or progress to serious disease.
  2. Latent TB can reactivate years later if immunity wanes.
  3. Active TB (post-primary/reactivation) typically presents in the lungs (pulmonary TB) or other organs (extrapulmonary TB).
• Multi-drug-resistant (MDR) TB: Resistance to rifampicin and isoniazid; more difficult to treat.

Types of Tuberculosis

1. Primary TB: Initial pulmonary infection, often asymptomatic but can be severe.
2. Latent TB: Dormant infection that can reactivate.
3. Post-primary (Reactivation) TB: Usually appears in the lung apices but can affect any organ.
4. Pulmonary TB: Infection within the lung tissue.
5. Extrapulmonary TB: Affects other sites (e.g. lymph nodes, bone, pericardium).
6. Miliary TB: Disseminated via the bloodstream, forming multiple tiny nodules in lungs (and often other organs).
7. Bovine TB: Caused by M. bovis, often via infected cow’s milk.
8. Multi-drug-resistant TB: TB strains resistant to at least rifampicin and isoniazid.

9.3 Risk Factors

1. Residence or Birth in High-Incidence Countries (e.g. parts of Asia, sub-Saharan Africa).
2. Social Factors: Overcrowding, homelessness, prison settings.
3. Substance Use: Smoking, alcohol or recreational drug misuse.
4. Medical Immunosuppression: HIV infection, high-dose steroids, diabetes mellitus, malnutrition.
5. Recent Immigration: Reactivation more likely after migration from endemic regions.

9.4 Clinical Features

9.4.1 General (Systemic)

• Subacute presentation over weeks or months.
• Fever, night sweats, malaise, anorexia, weight loss.

9.4.2 Pulmonary TB

• Cough (dry or productive), possibly >2–3 weeks.
• Haemoptysis (sometimes severe).
• Dyspnoea if disease is extensive.
• Examination may reveal crepitations or bronchial breathing, but can often be normal.

9.4.3 Extrapulmonary TB

• Depends on the site involved (see examples below):
  • Lymph nodes (cervical, mediastinal, etc.): “Cold” painless enlargements; can form sinuses.
  • Pleura: Unilateral lymphocytic exudate (pleural effusion).
  • Bone and joints (e.g. Pott’s disease of the spine): Pain, vertebral destruction.
  • Genitourinary tract: Sterile pyuria, haematuria.
  • CNS: Tuberculous meningitis (headache, focal neurology, confusion), tuberculomas.
  • Miliary TB: Widespread disseminated lesions with small “millet seed”–like nodules in the lungs; high mortality if untreated.

9.5 Diagnostic Approach

1. Clinical Suspicion
   • High index of suspicion in patients from endemic areas or with immunosuppression.
2. Chest X-ray
   • Upper lobe patchy or nodular shadowing, cavitation, hilar/mediastinal lymphadenopathy.
   • Miliary TB: Diffuse micronodular pattern.
3. Sputum Tests
   • Acid-fast bacilli (AFB) smear: Three early-morning samples (positive in ~50% of active pulmonary TB).
   • Sputum culture: More sensitive (70–80% positive); allows drug sensitivity testing, but may take up to 6 weeks.
   • Nucleic acid amplification tests (NAAT): Rapid identification of M. tuberculosis and rifampicin resistance.
4. Tests for Latent TB
   • Mantoux (Tuberculin) skin test: Induration indicates prior exposure or vaccination.
   • Interferon-gamma release assays (IGRA): More specific, not confounded by BCG vaccination.
   • Positive tests do not distinguish latent from active disease.
5. Biopsy / Fluid Samples (if extrapulmonary)
   • Lymph node, pleural fluid, bone, or other affected sites for histology (caseating granulomas) and culture.
6. Differential Diagnosis
   • Subacute infections (fungal, Nocardia, or others).
   • Cavitating lesions (malignancy, vasculitis, abscess).
   • Sarcoidosis, allergic bronchopulmonary aspergillosis (ABPA).

9.6 Immediate Management

1. Isolation and Notification
   • Infectious pulmonary TB: minimise contact with susceptible individuals.
   • Statutory notification to public health authorities in many countries.
2. Empirical Treatment
   • Indicated if clinical suspicion is high, especially in severe presentations or risk of dissemination, pending culture results.

9.7 Long-Term Management

9.7.1 Standard Anti-TB Therapy

• 2 months of Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RIPE)
• Followed by 4 months of Rifampicin + Isoniazid
• Total = 6 months for uncomplicated pulmonary TB.

Key considerations

• Pyridoxine (vitamin B6) given with isoniazid to prevent neuropathy.
• Monitor liver function due to potential hepatotoxicity (especially with isoniazid and pyrazinamide).
• Directly Observed Therapy (DOT) may be used in high-risk groups (e.g. previous treatment failure, homelessness, ongoing drug misuse).

9.7.2 Exceptions

• CNS TB (e.g. meningitis, tuberculomas) or pericardial TB: Extended treatment ≥12 months + corticosteroidsto reduce inflammation and fibrosis.
• Multidrug-resistant TB (MDR-TB): Requires prolonged regimens (often >18 months) with second/third-line agents.

9.7.3 Latent TB Infection (LTBI)

• Isoniazid for 6 months, or
• Isoniazid + Rifampicin for 3 months
• Reduces risk of future active disease.

9.8 Prognosis / Complications

• High cure rate (≈95%) with full, correctly supervised treatment.
• Failure to improve may reflect non-adherence, drug resistance, or misdiagnosis.
• Drug-resistant TB (particularly MDR- and XDR-TB) significantly increases mortality and complexity of treatment.
• Long-term sequelae:
  • Residual lung changes: apical scarring, bronchiectasis, mycetomas in old cavities.
  • Pleural thickening or adhesions, leading to restrictive changes.

10. Non-Tuberculous Mycobacteria

10.1 Epidemiology

• Uncommon infections: NTM infections occur far less frequently than tuberculosis in most regions.
• Environmental Reservoirs: Found in soil and water, leading to occasional human exposure.
• Typically affect individuals with pre-existing lung disease or those immunocompromised (especially advanced HIV).

10.2 Aetiology

• Caused by environmental mycobacteria:
  • Mycobacterium kansasii
  • M. xenopi
  • M. avium / M. intracellulare (often collectively referred to as MAC—Mycobacterium avium complex)
  • M. fortuitum
• These species are non-tuberculous (i.e. not Mycobacterium tuberculosis or M. bovis).

10.3 Risk Factors

1. Pre-existing Lung Disease
   • Chronic obstructive pulmonary disease (COPD)
   • Bronchiectasis
   • Cystic fibrosis
   • Previously damaged lung parenchyma
2. Immunosuppression
   • HIV infection (especially low CD4 counts)
   • Long-term immunosuppressive medications (e.g. high-dose steroids, anti-TNF therapy)
   • Post-transplant patients
3. Environmental Exposure
   • Frequent contact with contaminated water or soil (though specific high-risk exposures are less well defined compared to TB).

10.4 Clinical Features

1. Pulmonary Disease
   • Macronodular or cavitating infections resembling pulmonary tuberculosis (e.g. upper lobe cavities).
   • Multiple small cavities/nodules and progressive bronchiectasis (especially in patients with underlying lung conditions).
2. Disseminated Disease
   • Occurs predominantly in severely immunocompromised individuals (e.g. advanced HIV).
   • May involve lungs, lymph nodes, bone marrow, and other organs.

10.5 Diagnostic Approach

1. Clinical and Radiological Evidence
   • Symptoms (e.g. chronic cough, haemoptysis, weight loss, night sweats).
   • Imaging showing cavities, nodules, or bronchiectatic changes.
2. Microbiological Confirmation
   • Sputum cultures for mycobacteria (often need multiple samples).
   • A single positive culture can merely indicate colonisation; diagnosing true NTM disease typically requires:
     • Two or more positive cultures from separate sputum samples
     • OR one positive culture from a sterile site (e.g. bronchoalveolar lavage, lung biopsy)
     • PLUS correlating clinical/radiological findings.
3. Distinction from Mycobacterium tuberculosis
   • Nucleic acid amplification tests (where available)
   • Growth characteristics on culture media
   • Drug-susceptibility testing

10.6 Immediate Management

• Supportive Care
  • Assess and stabilise any acute respiratory compromise.
  • Optimise treatment of underlying lung conditions (e.g. bronchodilators for COPD, airway clearance for bronchiectasis).
• Assess Immunosuppression
  • Identify and address reversible causes (e.g. better HIV control with antiretroviral therapy if needed).
  • Consider reducing immunosuppressive drugs if clinically feasible.

(True “immediate management” is often limited, as NTM infections are typically subacute; the mainstay is careful evaluation before long-term therapy.)

10.7 Long-Term Management

1. Prolonged Antibiotic Therapy
   • Regimens depend on the specific NTM species and local resistance patterns.
   • Often involve combinations of antimycobacterial drugs, macrolides (e.g. clarithromycin), ethambutol, and/or aminoglycosides.
   • Treatment can last months to over a year.
2. Monitoring Response
   • Repeat sputum cultures to confirm clearance or reduced bacterial load.
   • Regular imaging (chest X-ray or CT) to assess resolution or progression of cavities and nodules.
   • Monitor for drug toxicity (e.g. aminoglycoside-related nephrotoxicity or ototoxicity).
3. Adjunctive Measures
   • Airway clearance techniques for bronchiectasis.
   • Smoking cessation and rehabilitation programmes where appropriate.

10.8 Prognosis / Complications

• Variable Treatment Response: Many patients experience poor or partial responses; infections can become chronic or progressive.
• High Mortality: In advanced disease, especially among the severely immunosuppressed (e.g. HIV with low CD4), mortality rates are significant.
• Relapse is possible if organisms are not fully eradicated or if immune function remains compromised.